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Biomedical subjects

J W Drysdale

Publications and source records attributed to J W Drysdale.

At least 19 recordsLinked to original sources
PubMed1990

Identification of two human ferritin H genes on the short arm of chromosome 6.

We have found by analyses of human-hamster hybrid cells that two human ferritin H genes lie near the locus of the iron storage disease idiopathic hemochromatosis on chromosome 6p. One of these genes was isolated and shown to be a processed pseudogene. Comparison of its sequence with those of other ferritin H pseudogenes indicates that they may be derived from a functional H gene other than that on chromosome 11.

Animals↗
PubMed1987

Human ferritin H and L sequences lie on ten different chromosomes.

In humans, the H (heavy) and L (light) chains of the iron-storage protein ferritin, are derived from multigene families. We have examined the chromosomal distribution of these H and L sequences by Southern analysis of hybrid cell DNA and by chromosomal in situ hybridization. Our results show that human ferritin H genes and related sequences are found on at least seven different chromosomes while L genes and related sequences are on at least three different chromosomes. Further, we have mapped the chromosomal location of expressed genes for human H and L ferritin chains and have found an H sequence which may be a useful marker for idiopathic hemochromatosis.

Animals↗
PubMed1985

Structural and functional relationships of human ferritin H and L chains deduced from cDNA clones.

We have isolated essentially full-length cDNA clones for human ferritin H and L chains from a human liver cDNA library. This allows the first comparison of H and L nucleotide and amino acid sequences from the same species as well as ferritin L cDNA sequences from different species. We conclude that human H and L ferritins are related proteins which diverged about the time of evolution of birds and mammals. We also deduce the secondary structure of the H and L subunits and compare this with the known structure of horse spleen ferritin. We find that residues involved in subunit interaction in shell assembly are highly conserved in H and L sequences. However, we find several interesting differences in H subunits at the amino acid residues involved in iron transport and deposition. These substitutions could account for known differences in the uptake, storage, and release of iron from isoferritins of different subunit composition.

Amino Acid Sequence↗
PubMed1985

Ferritin H and L chains are derived from different multigene families.

This paper explores the complexity of human ferritin H and L genes. We show that essentially full-length cDNA clones for human ferritin H and L chains do not cross-hybridize under moderate stringency conditions and present the first comparisons of H and L mRNAs and genes from the same species. Northern blot analyses indicate that the H and L mRNAs each contain about 1100 nucleotides. Subprobe analyses of Southern blots show that both H and L genes exist as multiple gene families. Both the 5' and 3' sequences of the H genes are heterogeneous, whereas the 3' end of the L gene is relatively conserved.

Base Sequence↗
PubMed1985

Complementarity between ferritin H mRNA and 28 S ribosomal RNA.

We have found an interesting complementarity in sequences of human ferritin H mRNA and 28 S ribosomal RNA. Immediately upstream of the initiating AUG in the ferritin mRNA is a stretch of 67 nucleotides which contains sequences complementary to several regions in 28 S RNA. One such region can form 55 base pairings with the 5' noncoding region of the ferritin H mRNA. Most of the complementarity is due to repeats of CCG in the ferritin mRNA and GGC in the ribosomal RNA. The regions of complementarity in the 28 S RNA appear to be expansion sequences that have arisen in the evolution of eukaryotic ribosomal RNA. We suggest that interaction of ferritin mRNA and 28 S RNA may function to regulate the stability and/or translatability of ferritin mRNA.

Animals↗
PubMed1985

Immunoreactivities of human isoferritins.

We have examined the immunoreactivities of antisera prepared against ferritins from human liver and HeLa cells to tissue ferritins and to individual isoferritins. In a radioimmune assay for HeLa ferritin the cross-reactivity of liver ferritin was about 2.5%. However, the apparent recovery of liver ferritin in the presence of different levels of HeLa ferritin was very much greater than that predicted from the measured cross-reactivity. This anomalous behaviour was eliminated by absorption of the HeLa antiserum with L-rich ferritins, suggesting that it represented interaction with common determinants in H and L subunits. The relative levels of H and L determinants measured by radioimmunoassay in individual isoferritins correlated with their relative contents of H and L subunits. However, in some parts of the isoferritin spectrum, the radioimmunoassay underestimated the H subunit content of L-rich isoferritins and overestimated the H subunit content of L-rich isoferritins and overestimated the H subunit content of H-rich isoferritins. This finding suggests differential expression of determinants in the various heteropolymers. These could arise from conformational changes leading to exposure or internalization of different determinants, or to recognition of determinants from certain subunit interactions.

Antibody Specificity↗
PubMed1980

Differential turnover of rat liver isoferritins.

Rat liver ferritins consist of families of isoferritins fashioned from different proportions of two subunit types, H and L. Iron administration alters both the absolute and the relative amounts of these isoferritins through an increase in L-rich forms. This phenotype change represents preferential synthesis of L-rich isoferritins together with a faster degradation of H-rich isoferritins. The turnover rates of isoferritins in the same liver are markedly different and vary progressively with subunit composition. The H and L subunits in individual isoferritins appear to turn over at similar rates, suggesting that the various isoferritins are degraded as intact shells rather than through exchange and degradation of subunits.

Animals↗
PubMed1978

On ferritin heterogeneity. Further evidence for heteropolymers.

Tissue ferritins from the horse, rat, and human consist of multiple isoferritins some of which are common to more than one tissue in the same individual. Subunit analyses indicate that the ferritins from all three species are similarly composed of only two types of subunit with an approximate Mr of 21,000 and 19,000, designated H and L. The relative amounts of these subunits vary progressively throughout the isoferritin spectrum. Amino acid analyses and tryptic peptide maps indicate that the H and L subunits have extensive sequence homologies and that both are species-specific. Both subunits have been identified as the primary products of apoferritin synthesis in a wheat germ lysate programmed by rat liver mRNA. These results substantiate our proposal (Adelman, T. G., Arosio, P., and Drysdale, J. W. (1975) Biochem. Biophys. Res. Commun. 63, 1056-1062) that tissue ferritins are not unique homopolymers but families of hybrid molecules consisting of different proportions of two subunit types.

Amino Acids↗
PubMed1977

Characterization of serum ferritin in iron overload: possible identity to natural apoferritin.

Serum ferritins from a patient with haemochromatosis and from a patient with transfusional siderosis were compared with tissue isoferritins on the basis of their iron content, isoferritin spectrum and immunological properties. Both serum ferritins had a low iron content and corresponded to only the most basic isoferritins in liver. The serum ferritins were very similar to the natural apoferritin from liver in all respects.

Apoferritins↗
PubMed1977

Immunologic differences in human isoferritins: implications for immunologic quantitation of serum ferritin.

Immunologic differences in several tissue isoferritin populations have been investigated using antibodies developed in rabbits against human liver ferritin and in guinea pigs against HeLa cell ferritin. Our results indicate that the quantity of ferritin measured by radioimmunoassays is markedly affected by the isoferritin and subunit composition of the ferritin sample as well as by the nature of the antiferritin antibodies. Possible applications for the selective quantitation of different serum ferritin populations are discussed.

Animals↗
PubMed1976

Structural and immunological relationships of isoferritins in normal and malignant cells.

Ferritins from normal adult human liver and heart were compared with ferritins from a lung carcinoma metastatic to liver and from HeLa cells on the basis of their isoferritin profiles, subunit composition, and immunological relationships. Each ferritin preparation gave different isoferritin profiles, but several contained common isoferritins. All of the tumor isoferritins had counterparts in the normal tissues. All ferritins contained similar subunits but in different proportions. Qualitative differences were demonstrable in some ferritins with antibodies to different tissue ferritins. These differences correlated with the subunit composition of the ferritins. By appropriate absorption, an antibody population was obtained that was apparently specific for one subunit type. Heart ferritin gave lines of apparent identity with the tumor ferritins with these antibodies. It is concluded that tumor ferritins are not tumor-specific antigens but correspond to isoferritins in normal adult heart.

Antibodies↗